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1.
Phys Chem Chem Phys ; 23(35): 19752-19759, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524302

RESUMO

The redox of silver on the surface of Ag nanoparticles (AgNPs) has received extensive attention because of its significant impact on the biological, physical and chemical properties of AgNPs and their applications. Here we demonstrate that the surface redox reaction of AgNPs in colloids may be investigated by the second harmonic generation (SHG) and two-photon luminescence (TPL) emission from the AgNPs. It was revealed that the oxidation of silver on the surface of AgNPs was accelerated upon femtosecond laser excitation, accompanied by a decrease in the SHG and TPL emissions from the AgNPs. The photon-induced reduction of oxidized silver on AgNPs and the formation of surface defects were also revealed by the changes in the SHG and TPL emissions. Size and morphology changes have not been detected by dynamic light scattering and TEM measurements. The changes in the UV-vis extinction spectra were also very weak compared with previous reports. However, the occurrence of redox reactions on the Ag surface upon femtosecond laser irradiation has been confirmed by multiple control experiments. This work demonstrates that SHG and TPL can sensitively probe the subtle structural change on the surface of AgNPs.

2.
J Mater Chem B ; 9(37): 7662-7673, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586153

RESUMO

We developed poly(vinyl alcohol-co-itaconic acid) (PV) hydrogels grafted with laminin-derived peptides that had different joint segments and several specific designs, including dual chain motifs. PV hydrogels grafted with a peptide derived from laminin-ß4 (PMQKMRGDVFSP) containing a joint segment, dual chain motif and cationic amino acid insertion could attach human pluripotent stem (hPS) cells and promoted high expansion folds in long-term culture (over 10 passages) with low differentiation rates, whereas hPS cells attached poorly on PV hydrogels grafted with laminin-α5 peptides that had joint segments with and without a cationic amino acid or on PV hydrogels grafted with laminin-ß4 peptides containing the joint segment only. The inclusion of a cationic amino acid in the laminin-ß4 peptide was critical for hPS cell attachment on PV hydrogels, which contributed to the zeta potential shifting to higher values (3-4 mV enhancement). The novel peptide segment-grafted PV hydrogels developed in this study supported hPS cell proliferation, which induced better hPS cell expansion than recombinant vitronectin-coated dishes (gold standard of hPS cell culture dishes) in xeno-free culture conditions. After long-term culture on peptide-grafted hydrogels, hPS cells could be induced to differentiate into specific lineages of cells, such as cardiomyocytes, with high efficiency.

3.
BMC Musculoskelet Disord ; 22(1): 728, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429080

RESUMO

BACKGROUND: Fragility fracture is associated with bone mineral density (BMD), and most databases used in related researches are instrument-matched. Little is known about the relationship between BMD and fragility fracture risk of native Chinese, especially using local databases as reference databases. OBJECTIVE: To investigate relationship between BMD and risk of fragility fracture in native China. METHODS: 3,324 cases, including 2,423 women (67.7 ± 8.9 years) and 901 men (68.4 ± 11.6 years) having radiological fragility fractures and 3,324 age- and gender-matched controls participated in the study. We measured BMD at posteroanterior spine and hip using dual-energy X-ray absorptiometry (DXA), calculated BMD measurement parameters based on our own BMD reference database. RESULTS: BMDs and mean T-scores were lower in case group (with clinical fragility) than in control group (without clinical fragility). In patients with fragility fractures, prevalence of lumbar osteoporosis, low bone mass, and normal BMD were 78.9 %, 19.3 %, and 1.8 %, respectively, in women, and 49.5, 44.8 %, and 5.7 %, respectively, in men. In hip, these prevalence rates were 67.2 %, 28.4 %, and 4.4 % in females, and 43.2 %, 45.9 %, and 10.9 % in males, respectively, showing differences between females and males. Multivariate Cox regression analysis showed that after adjusting age, height, weight, and body mass index, fracture hazard ratio (HR) increased by 2.7-2.8 times (95 % CI 2.5-3.1) and 3.6-4.1 times (95 %CI 3.0-5.1) for women and men respectively with decreasing BMD parameters. In both sexes, risk of fragility fracture increased approximately 1.6-1.7 times (95 % CI 1.5-1.8) for every 1 T-score reduction in BMD. CONCLUSIONS: Risk of clinical fragility fracture increases with decreasing BMD measurement parameters and anthropometric indicators in native China, and fracture HR varies from gender and site.


Assuntos
Densidade Óssea , Fraturas Ósseas , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Vértebras Lombares , Masculino
4.
Nat Commun ; 12(1): 5072, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417473

RESUMO

In vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.


Assuntos
Bioimpressão , Cateteres , Imãs/química , Robótica , Animais , Linhagem Celular , Elasticidade , Condutividade Elétrica , Humanos , Hidrogéis/química , Fígado/diagnóstico por imagem , Ratos Sprague-Dawley , Suínos , Tomografia Computadorizada por Raios X , Viscosidade
5.
Huan Jing Ke Xue ; 42(8): 4015-4023, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309288

RESUMO

Vertically tiered soil profiles, comprising miscellaneous fill (S1), plain fill (S2), silty clay (S3), and completely weathered slate (S4), were collected from a zinc smelter site in Zhuzhou City, Hunan Province, and their Cd and Pb adsorption characteristics were examined. Static batch experiments were conducted with different initial Cd and Pb solution concentrations, at temperatures of 288-308 K and pH values of 2-6. The results showed that a pseudo first-order model could be fitted to the kinetics of Cd/Pb adsorption in these soils. The soil profiles had a large retention capacity for Cd and Pb. The Cd and Pb adsorption isotherms for these soils conformed to the Freundlich isotherm, with maximum adsorption at 298 K of 2097-4504 mg ·kg-1 for Cd and 4376-10564 mg ·kg-1 for Pb, based on the Langmuir isotherm. The adsorption capacity of Cd and Pb increased with an increase in initial pH and temperature. The Cd and Pb adsorption process were a spontaneous physical and chemical process, and the soil profiles were ranked by their Cd and Pb adsorption capacities in the following order:completely weathered slate (S4)>miscellaneous fill (S1)>silty clay (S3)>plain fill (S2). The variation in adsorption capacities resulted from the differences in physical and chemical properties of the soil, mainly Fe/Al content and cation exchange capacity. Fourier transform infrared and SEM-EDS analysis showed that the main adsorption mechanism is the exchange of Cd and Pb with Fe/Al, while -OH/C=O sites in soils were the predominant adsorption sites for Cd and Pb. In the study area, exogenous Cd and Pb discharged by smelting activity accumulated predominantly in surface soil, and their concentration gradually decreased with depth. These results provide a scientific basis for the prevention and control of heavy metal pollution in the soil and groundwater of a smelting site.


Assuntos
Poluentes do Solo , Solo , Adsorção , Cádmio/análise , Cidades , Concentração de Íons de Hidrogênio , Cinética , Chumbo , Poluentes do Solo/análise , Zinco/análise
6.
Front Endocrinol (Lausanne) ; 12: 678309, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276559

RESUMO

Irisin, a PGC1α-dependent myokine, was once believed to have beneficial effects induced by exercise. Since its first discovery of adipose browning in 2012, multiple studies have been trying to explore the metabolic functions of irisin, such as glucose and lipid metabolism. However, recently many studies with irisin concentration measuring were doubt for methodological problems, which may account for the continuous inconsistencies. New tools like recombinant irisin and gene-knockout mice are required to reconfirm the questioned functions of irisin. In this paper, we make a critical introduction to the latest researches concerning the relationship between irisin and coronary heart disease, which includes atherosclerosis, stable angina pectoris and acute coronary syndromes. These studies provided various controversial evidence of short and long-term monitoring and therapeutic effect from molecular cellular mechanisms, in vivo experiments and epidemiological investigation. But with ambiguities, irisin still has a long way to go to identify its functions in the clinical management.

7.
EBioMedicine ; 69: 103441, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34166980

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is a group of heterogeneous hematologic malignancies correlates with poor prognosis. It is important to identify biomarkers for effective treatment of AML. Kinases participate in many regulatory pathways and biological activities in AML. Previous studies demonstrated that MAP4K1, a serine/threonine kinase, was associated with immune regulation and cancer progression. However, its role and mechanism in acute myeloid leukemia (AML) have not been explored. METHODS: RNA-seq profiling was performed for Homoharringtonine (HHT)-resistant and Homoharringtonine (HHT)-sensitive cell lines. Bioinformatic tools were used for differential analysis. Cell culture and transfection, Cell proliferation, apoptosis and Cell cycle assay, Quantitative RT-PCR, and Western blotting analysis were used to explore biological phenotypes in vitro. FINDINGS: We found that MAP4K1 was highly expressed in HHT-induced resistant AML cell lines. In addition, overexpression of MAP4K1 in AML cells induced resistance of AML cells against HHT. Not only that, the findings of this study showed that overexpression of MAP4K1 was an independent risk factor that predicts poor prognosis of AML. Further, In vitro studies showed that MAP4K1 modulated cell cycle through MAPK and DNA damage/repair pathways. Therefore, MAP4K1 is a potential target for developing therapies for AML. INTERPRETATION: This study demonstrates that MAP4K1 not only regulates HHT resistance but also independently predicts AML prognosis. In addition, understanding the regulatory mechanism of MAP4K1 reveals novel treatment strategies for resistant and refractory AML. Fundings: This work was supported by the National Natural Science Foundation of China (NSFC) (Grant No.81800199, 81670124, 82070118) and the Natural Science Foundation of Zhejiang Province (LY20H080008).


Assuntos
Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Antineoplásicos Fitogênicos/toxicidade , Apoptose , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Dano ao DNA , Reparo do DNA , Mepesuccinato de Omacetaxina/toxicidade , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Células THP-1 , Transcriptoma
8.
Stem Cell Res Ther ; 12(1): 340, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112266

RESUMO

BACKGROUND: The preservation or restoration of ß cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. METHODS: This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. RESULTS: After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. CONCLUSION: One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet ß cell preservation during the first year after diagnosis compared to standard treatment alone. TRIAL REGISTRATION: ChiCTR2100045434 . Registered on April 15, 2021-retrospectively registered, http://www.chictr.org.cn/.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Adulto , Diabetes Mellitus Tipo 1/terapia , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Estudos Prospectivos , Cordão Umbilical
9.
Artigo em Inglês | MEDLINE | ID: mdl-34086584

RESUMO

This article develops a communication-efficient algorithm to solve the stochastic optimization problem defined over a distributed network, aiming at reducing the burdensome communication in applications, such as distributed machine learning. Different from the existing works based on quantization and sparsification, we introduce a communication-censoring technique to reduce the transmissions of variables, which leads to our communication-censored distributed stochastic gradient descent (CSGD) algorithm. Specifically, in CSGD, the latest minibatch stochastic gradient at a worker will be transmitted to the server if and only if it is sufficiently informative. When the latest gradient is not available, the stale one will be reused at the server. To implement this communication-censoring strategy, the batch size is increasing in order to alleviate the effect of stochastic gradient noise. Theoretically, CSGD enjoys the same order of convergence rate as that of SGD but effectively reduces communication. Numerical experiments demonstrate the sizable communication saving of CSGD.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34146130

RESUMO

PURPOSE: Localizing the source of ectopic adrenocorticotropic hormone secretion (EAS) is challenging. This study compared the diagnostic value of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT in tumors with EAS. METHODS: Thirty-six patients with a suspicion of EAS were enrolled to undergo both 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT within 4 weeks for comparison. Twenty-three underwent surgical resection or biopsy. Immunohistochemical staining for SSTR2 and Ki-67 was performed to correlate with 68Ga-DOTATATE uptake and 18F-FDG uptake, respectively. RESULTS: EAS tumors were observed in 20/23 patients. Among the 20 patients with histologically proven EAS tumors, 68Ga-DOTATATE PET/CT correctly identified the tumor in 15 (75.0%), with an SUVmax ranging from 1.4 to 20.7 (6.7 ± 5.5). 18F-FDG PET/CT correctly identified the tumor in 12 (60.0%) patients, with an SUVmax ranging from 1.8 to 10.0 (4.0 ± 2.1). Moreover, 68Ga-DOTATATE PET/CT unmasked the sources of EAS in 6 patients with negative 18F-FDG uptake, and 18F-FDG PET/CT unmasked the sources in 3 patients with negative 68Ga-DOTATATE uptake, resulting in EAS tumors being identified in 18 (90%) patients by combining 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT. CONCLUSIONS: 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT are complementary in localizing and discriminating the source of EAS. 68Ga-DOTATATE PET/CT combined with 18F-FDG PET/CT had higher detection rate than each alone. TRIAL REGISTRATION: 68Ga-DOTATATE PET/CT in Neuroendocrine Tumors (NCT04041882) URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04041882.

11.
Front Endocrinol (Lausanne) ; 12: 671566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163437

RESUMO

Diabetic nephropathy (DN) is one of the most common diabetes mellitus (DM) microvascular complications, which always ends with end-stage renal disease (ESRD). Up to now, as the treatment of DN in clinic is still complicated, ESRD has become the main cause of death in diabetic patients. Mesenchymal stem cells (MSCs), with multi-differentiation potential and paracrine function, have attracted considerable attention in cell therapy recently. Increasing studies concerning the mechanisms and therapeutic effect of MSCs in DN emerged. This review summarizes several mechanisms of MSCs, especially MSCs derived exosomes in DN therapy, including hyperglycemia regulation, anti-inflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection. We also emphasize the limitation of MSCs application in the clinic and the enhanced therapeutic role of pre-treated MSCs in the DN therapy. This review provides balanced and impartial views for MSC therapy as a promising strategy in diabetic kidney disease amelioration.

12.
Aging (Albany NY) ; 13(7): 10468-10489, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33820874

RESUMO

We described the spatial and temporal trends of the annual leukemia incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2017. Leukemia case numbers and age-standardized rates (ASRs) were extracted from the Global Burden of Disease (GBD) study 2017. The estimated annual percentage change (EAPC) in the ASR was calculated using a generalized linear model with a Gaussian distribution. The risk factors for death and DALYs due to leukemia were estimated within the comparative risk assessment framework of the GBD study. Globally, the prevalence, age-standardized prevalence rate (ASPR), and EAPC in leukemia cases in 2017 were 2.43 (95% uncertainty interval (UI) 2.19 to 2.59) million, 32.26 (95% UI 29.02 to 34.61), and 0.22% (95% CI 0.13 to 0.31, P<0.01), respectively, during 1990-2017. The trends of the age-standardized incidence, deaths, and DALY rate all significantly decreased globally. The burden of leukemia was higher in males than in female. An increasing leukemia burden was found in high-middle-sociodemographic index (SDI) countries and territories. The burden of leukemia tended to be lower in high-SDI regions than that in lower SDI regions. The rapid increases in the prevalent cases and prevalence rate of leukemia is urgent to be solved in the future.


Assuntos
Carga Global da Doença/tendências , Leucemia/epidemiologia , Humanos
13.
J Transl Med ; 19(1): 181, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33926484

RESUMO

BACKGROUND: Fatty acid oxidation (FAO) provides an important source of energy to promote the growth of leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme of the essential step of FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as a potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted to explore the prognostic value of CPT1a expression and possible treatment strategies with CPT1a inhibitor on acute myeloid leukemia (AML). METHODS: The expression of CPT1a in 325 cytogenetically normal AML (CN-AML) patients was evaluated using RT-PCR. The combination effects of ST1326 and ABT199 were studied in AML cells and primary patients. MTS was used to measure the cell proliferation rate. Annexin V/propidium iodide staining and flow cytometry analysis was used to measure the apoptosis rate. Western blot was used to measure the expression of Mcl-1. RNAseq and GC-TOFMS were used for genomic and metabolic analysis. RESULTS: In this study, we found AML patients with high CPT1a expression (n = 245) had a relatively short overall survival (P = 0.01) compared to patients in low expression group (n = 80). In parallel, downregulation of CPT1a inhibits proliferation of AML cells. We also conducted genomic and metabolic interactive analysis in AML patients, and found several essential genes and pathways related to aberrant expression of CPT1a. Moreover, we found downregulation of CPT1a sentitized BCL-2 inhibitor ABT199 and CPT1a-selective inhibitor ST1326 combined with ABT199 had a strong synergistic effect to induce apoptosis in AML cells and primary patient blasts for the first time. The underlying synergistic mechanism might be that ST1326 inhibits pGSK3ß and pERK expression, leading to downregulation of Mcl-1. CONCLUSION: Our study indicates that overexpression of CPT1a predicts poor clinical outcome in AML. CPT1a-selective inhibitor ST1326 combined with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML.


Assuntos
Leucemia Mieloide Aguda , Apoptose , Linhagem Celular Tumoral , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Prognóstico , Sulfonamidas
14.
Biomed Res Int ; 2021: 6661588, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728337

RESUMO

Aim: We aimed to perform a meta-analysis to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infections (UTIs) after urodynamic studies (UDS). Methods: We conducted a systematic search of PubMed, Web of Science, Ovid, Elsevier, ClinicalKey, Embase, Cochrane Library, Medline, and Wiley Online Library. Randomized controlled trials (RCTs) comparing the effectiveness of prophylactic antibiotics with placebo or no treatment in preventing UTI after UDS were included. Two reviewers extracted data independently, and RevMan 5.3 software was used to analyze relative risk (RR) with 95% confidence intervals (CI). Heterogeneity was assessed by the Q test and I 2 test. Results: The final meta-analysis included 1829 patients in 13 RCTs. Compared with the placebo or no treatment group, prophylactic antibiotics could significantly reduce the risk of bacteriuria (RR = 0.42, 95% CI: 0.30-0.60) and the risk of symptomatic UTI (RR = 0.65, 95% CI: 0.48-0.88). In addition, there was no statistically significant difference in the risk of adverse events (RR = 4.93, 95% CI: 0.61-40.05). No significant heterogeneity or publication bias was found in this study. Conclusions: Current evidence showed that prophylactic antibiotics could reduce the risk of asymptomatic bacteriuria and symptomatic UTI after UDS without increasing the incidence of adverse events.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Bacteriúria/prevenção & controle , Infecções Urinárias/prevenção & controle , Urodinâmica , Bacteriúria/fisiopatologia , Feminino , Humanos , Masculino , Infecções Urinárias/fisiopatologia
15.
BMC Med ; 19(1): 28, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33517886

RESUMO

BACKGROUND: Although there are many clinical and molecular biomarkers in acute myeloid leukemia (AML), the novel and reliable biomarkers are still required to predict the overall survival at the time of disease diagnosis. METHODS: In order to identify independent predictors, we firstly selected 60 cytogenetically normal AML (CN-AML) patients using the propensity score analysis to balance the confounders and performed circular RNA (circRNA) sequencing. Next, one outcome related to circRNA was selected and validated in the independent cohort of 218 CN-AML patients. We then constructed circRNA-miRNA-mRNA regulated network and performed cellular metabolomic analysis to decipher the underlying biological insights. RESULTS: We identified 308 circRNAs as independent candidate predictors of overall survival. Hsa_circ_0075451 expression was validated as an independent predictor with a weak predictive ability for overall survival. The regulated network of this circular RNA indicated 84 hub genes that appear to be regulated by 10 miRNAs sponged by hsa_circ_0075451. The regulatory axis of hsa_circ_0075451 -| miR-330-5p/miR-326 -| PRDM16 was validated by the dual luciferase report assay, fluorescence in situ hybridization, and ShRNA interference assay. CONCLUSIONS: Our data demonstrates that hsa_circ_0075451 expression may independently contribute to the poor prognosis of AML and present a novel therapeutic target.


Assuntos
Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , RNA Mensageiro/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente/métodos , Leucemia Mieloide Aguda/genética , Masculino , Prognóstico , RNA/metabolismo , RNA Mensageiro/metabolismo , Análise de Sequência de RNA
16.
Cell Prolif ; 54(3): e12995, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33522648

RESUMO

INTRODUCTION: It is important to prepare 'hypoimmunogenic' or 'universal' human pluripotent stem cells (hPSCs) with gene-editing technology by knocking out or in immune-related genes, because only a few hypoimmunogenic or universal hPSC lines would be sufficient to store for their off-the-shelf use. However, these hypoimmunogenic or universal hPSCs prepared previously were all genetically edited, which makes laborious processes to check and evaluate no abnormal gene editing of hPSCs. METHODS: Universal human-induced pluripotent stem cells (hiPSCs) were generated without gene editing, which were reprogrammed from foetal stem cells (human amniotic fluid stem cells) with mixing 2-5 allogenic donors but not with single donor. We evaluated human leucocyte antigen (HLA)-expressing class Ia and class II of our hiPSCs and their differentiated cells into embryoid bodies, cardiomyocytes and mesenchymal stem cells. We further evaluated immunogenic response of transient universal hiPSCs with allogenic mononuclear cells from survival rate and cytokine production, which were generated by the cells due to immunogenic reactions. RESULTS: Our universal hiPSCs during passages 10-25 did not have immunogenic reaction from allogenic mononuclear cells even after differentiation into cardiomyocytes, embryoid bodies and mesenchymal stem cells. Furthermore, the cells including the differentiated cells did not express HLA class Ia and class II. Cardiomyocytes differentiated from transient universal hiPSCs at passage 21-22 survived and continued beating even after treatment with allogenic mononuclear cells.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Fetais/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Pluripotentes/citologia , Corpos Embrioides/citologia , Edição de Genes/métodos , Humanos , Miócitos Cardíacos/citologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-33497344

RESUMO

In distributed learning and optimization, a network of multiple computing units coordinates to solve a large-scale problem. This article focuses on dynamic optimization over a decentralized network. We develop a communication-efficient algorithm based on the alternating direction method of multipliers (ADMM) with quantized and censored communications, termed DQC-ADMM. At each time of the algorithm, the nodes collaborate to minimize the summation of their time-varying, local objective functions. Through local iterative computation and communication, DQC-ADMM is able to track the time-varying optimal solution. Different from traditional approaches requiring transmissions of the exact local iterates among the neighbors at every time, we propose to quantize the transmitted information, as well as adopt a communication-censoring strategy for the sake of reducing the communication cost in the optimization process. To be specific, a node transmits the quantized version of the local information to its neighbors, if and only if the value sufficiently deviates from the one previously transmitted. We theoretically justify that the proposed DQC-ADMM is capable of tracking the time-varying optimal solution, subject to a bounded error caused by the quantized and censored communications, as well as the system dynamics. Through numerical experiments, we evaluate the tracking performance and communication savings of the proposed DQC-ADMM.

19.
Thromb Haemost ; 121(2): 192-205, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32961571

RESUMO

Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, has a favorable safety profile in patients with B cell-related malignancies. A primary adverse effect of ibrutinib is thrombocytopenia in the early stages of treatment, but platelet counts increase or recover as treatment continues. Currently, the effects of ibrutinib on megakaryopoiesis remain unclear. In this study, we investigated the mechanism by which ibrutinib induces thrombocytopenia using cord blood CD34+ hematopoietic stem cells (HSCs), a human megakaryoblastic cell line (SET-2), and C57BL/6 mice. We show that treatment with ibrutinib can suppress CD34+ HSC differentiation into megakaryocytes (MKs) and decrease the number of colony-forming unit-MKs (CFU-MKs). The ibrutinib-dependent inhibition of early megakaryopoiesis seems to mainly involve impaired proliferation of progenitor cells without induction of apoptosis. The effects of ibrutinib on late-stage megakaryopoiesis, in contrast to early-stage megakaryopoiesis, include enhanced MK differentiation, ploidy, and proplatelet formation in CD34+ HSC-derived MKs and SET-2 cells. We also demonstrated that MK adhesion and spreading, but not migration, were inhibited by ibrutinib. Furthermore, we revealed that integrin αIIbß3 outside-in signaling in MKs was inhibited by ibrutinib. Consistent with previous clinical observations, in C57BL/6 mice treated with ibrutinib, platelet counts decreased by days 2 to 7 and recovered to normal levels by day 15. Together, these results reveal the pathogenesis of ibrutinib-induced transient thrombocytopenia. In conclusion, ibrutinib suppresses early megakaryopoiesis, as evidenced by inhibition of MK progenitor cell proliferation and CFU-MK formation. Ibrutinib enhances MK differentiation, ploidy, and proplatelet formation, while it impairs integrin αIIbß3 outside-in signaling.

20.
World J Urol ; 39(5): 1597-1605, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32613324

RESUMO

PURPOSE: Refractory lower urinary tract symptoms (LUTS) coexisting with lumbar disc hernia (LDH) have been shown to resolve following LDH surgery, implying that LDH causes these LUTS. The purpose of this study was to report outcomes in patients with refractory LUTS and LDH following non-surgical treatment targeting LDH. METHODS: A retrospective cohort study was conducted using outpatient data collected at Tongji Hospital, China, between 2016 and 2018. This study included 131 adult patients with refractory LUTS and LDH. Patients were stratified into two groups. Group A underwent non-surgical treatment for LDH plus pharmacological treatment for LUTS. Group B underwent only pharmacological treatment for LUTS. The International Prostate Symptom Score (IPSS), the IPSS quality of life (QoL) score, and uroflowmetry were used to evaluate outcomes. RESULTS: In group A, following treatment, the maximum flow rate (Qmax) increased by 3.92 ml/s (p < 0.001), the IPSS reduced by 5.99 points (p < 0.001), and the QoL score decreased by 1.51 points (p < 0.001). In group B, the Qmax increased by 0.09 ml/s (p = 0.833), the IPSS reduced by 0.72 points (p = 0.163), and the QoL score decreased by 0.07 points (p = 0.784). CONCLUSIONS: LUTS can be relieved by a combination of pharmacological treatment for LUTS and non-surgical treatment for LDH in some refractory LUTS patients with LDH. MRI is recommended for these patients.

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